Evaluation of morphine, methadone, digoxin, and dronabinol poisoning during the years 2017 to 2019 in Ilam, Iran

Background: Every year, drug poisoning is the most prevalent reason for referring patients to medical centers. This study aimed to evaluation of morphine, methadone, digoxin, and dronabinol poisoning in Shahid Mostafa Khomeini Hospital in Ilam. Methods: In this In this Cross-sectional study, patient samples suspected of morphine, methadone, digoxin, and dronabinol poisoning referred to the toxicology laboratory of Ilam University of Medical Sciences were analyzed using the HPLC method, and the results were analysed using SPSS software. Results: Results showed that the percentage of drug use is greater in men than in women. The highest percentage of morphine and methadone poisonings were detected in those under the age of 40, whereas the highest percentage of digoxin poisonings were recorded in those over the age of 80. As a result, the average age of digoxin users was substantially greater in men than in women. Methadone consumers showed significantly greater blood levels than others. In addition, there was a significant difference (P<0.01) in blood levels between men and women who used morphine. Conclusion: In general, it is important to understand the status of drug poisoning with drugs such as morphine, methadone, digoxin, and dronabinol, as well as the prognosis associated with the treatment process of such poisoning.

According to the statistics of the Forensic Medicine Organization in 2016, over 5,812 individuals died in Iran as a result of drug, toxins, and carbon monoxide poisoning, with drug poisoning having the greatest mortality rate (10,11).
Methadone is a morphine-like pain reliever with a prolonged half-life of 25 to more than 52 hours. It alleviates withdrawal symptoms in those addicted to heroin or other narcotics. However, overdose might result in serious adverse effects or even die (16). Death from methadone poisoning is frequently caused by immune system suppression, while cardiac arrhythmias account for a large proportion of deaths.
It involves nausea, lethargy, and drowsiness, and if appropriate treatment is not provided, the child may develop sleep apnea and even death (17,18).
Digoxin is a cardiac glycoside with a positive inotropic effect in the heart muscle that increases the intracellular concentration of sodium, decreases the cytoplasmic potassium, and finally increases the calcium required for the contractile proteins of the heart and increases strength by inhibiting the pump-ATPase Na+/K-.Myocardial contraction is used in patients with chronic congestive heart failure, atrial flutter, and acute atrial paroxysmal tachycardia (PAT) (19,20).
Because the therapeutic and toxic doses of digoxin are very close to each other and have a narrow therapeutic index, small changes in serum digoxin levels can lead to severe intoxication; therefore, periodic evaluation of serum digoxin levels during treatment for prevention of poisoning is very important (21,22).

Dronabinol
is a hallucinogenic isomer of tetrahydrocannabinol (THC), which is the major and most active isomer found in the Cannabis sativa L. plant, is also a pressing concern for global mental health (23 digestive symptoms caused by drug overdose and were referred to the poisoning department of the hospital. Also written consent was obtained from the patients participating in the study and assurance that their personal information will remain confidential. Results are reported based on µg/mL.
Since these four drugs have many medicinal uses and the possibility of poisoning with them is high, they were chosen.
Above the standard level of serum level of any drug in the blood, the criterion of blood poisoning was considered. Tetrahydrocannabinol assay: THC was extracted from plasma samples using protein precipitation with cold acetonitrile and liquid-liquid extraction with n-hexane.
Following centrifugation, the upper organic layer was recovered and dried before being reconstituted in acetonitrile.
An aliquot of 30 µl was injected into the HPLC column.
The column temperature was set to 55 °C with a flow rate of 1 ml/min and a run time of 20 minutes. Both cannabis and the reference standard (4, 4-dichlorodiphenyltrichloroethane, DDT) were identified at 220 nm (22). A total of 41 tetrahydrocannabinol samples were tested for the presence of dronabinol.
Digoxin assay: The procedure established in the previous study was used to extract digoxin from plasma samples (23).
In brief, the plasma sample was extracted using chloroformisopropanol (9: l) after a pre-wash with isooctane to eliminate endogenous compounds in order to recover maximum digoxin (70%). Using digitoxigenin as the internal standard, the calibration curve was linear (r = 0.9999) across the range of 0.5-4 ng/ml of digoxin in plasma (23). The presence of digoxin was determined in 32 samples.

Instrumentation and chromatographic analysis:
Knauer's PLATINblueRP-HPLC system (Knauer company, Germany) was used to analyze the samples.The separation was carried out using Eurospher II 100-5 C18,250 × 4.6 mm column.

Statistical analysis:
The Mann-Whitney test was used to analyze the data using SPSS statistical software. The columns were categorized according to the IQR Median.The data were presented as mean ± SD, with a p value less than 0.05 considered significant.

Results
The     (29). As well asThe existence of underlying issues such as social, cultural, economic, psychological, and fluency problems, and especially drug addiction in any society can lead to intentional (34). Results of the current study showed that the majority of use drugs were male, which is consistent with the findings of Aryaie and Burillo studies (35)(36)(37). However, in Fazlohah's studies, the ratio of women to males was greater, which is contradictory (25). According to statistics, men had the biggest number of accidental poisonings, while women had the highest number of suicide attempts (38).
In various age groups, the type of morphine and methadone drug intoxication with digoxin and dronabinol was significantly different. Figure 1 depicts the highest and lowest age ranges for digoxin and dronabinol poisoning. Aging is a risk factor for digoxin toxicity. In this context, Baharvand (39) established a correlation between serum digoxin levels and In contrast, the majority of the poisonings were caused by methadone pills combined with suicidal intent (27).
Morphine is rapidly absorbed from the GI tract, has a bioavailability of around 43%, and is significantly affected by first-pass hepatic metabolism. It spreads throughout the body, with the liver, kidneys, lungs, and spleen being the most affected. More than 13% of a dose is conjugated in the faeces, with the balance conjugated in the urine (47). The principal complication of morphine is respiratory failure caused by direct CNS depression, which can eventually progress to apnea or total respiratory arrest (48,49).
The finding showed that the quantity of morphine in the blood and muscles ranged from 0. The most common symptom among poisoned patients is loss of consciousness, whereas respiratory distress is the least common (52).
Although chemical and herbal medicines can be beneficial in the treatment of diseases and disorders (53)(54)(55), such drugs have side effects, are toxic in high doses, and cause poisoning (49)(50)(51)(52)(53)(54). In recent years, drug poisoning, especially drugs such as morphine, methadone, digoxin, and dronabinol, has become common in Ilam province. Therefore, we decided to study drug poisoning in a seroepidemiological way to prevent serious complications and treat them by timely diagnosis of such poisonings. The extent of opioid analgesics use varies widely in the Iran. Variation in the availability of opioid analgesics is related to the spatial distribution of drug poisoning mortality. So, epidemiological information in a regional form leads to the rational use of resources for the prevention and control of poisoning. Also early prevention, as well as informing and educating people, can be very helpful.